Loss of SIRT2 leads to axonal degeneration and locomotor disability associated with redox and energy imbalance.

Sirtuin 2 (SIRT2) is a member of a family of NAD + -dependent histone deacetylases (HDAC) that play diverse roles in cellular metabolism and especially for aging process. SIRT2 is located in the nucleus, cytoplasm, and mitochondria, is highly expressed in the central nervous system (CNS), and has be...

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Autores: Fourcade S, Morató L, Parameswaran J, Ruiz M, Ruiz-Cortés T, Jové M, Naudí A, Martínez-Redondo P, Dierssen M, Ferrer I, Villarroya F, Pamplona R, Vaquero A, Portero-Otín M, Pujol A
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Fundació Sant Joan de Déu
Repositorio:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
OAI Identifier:oai:fsjd.fundanetsuite.com:p13070
Acceso en línea:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=13070
Access Level:acceso abierto
Palabra clave:aging, axonal degeneration, mitochondria, redox dyshomeostasis, sirtuin
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spelling Loss of SIRT2 leads to axonal degeneration and locomotor disability associated with redox and energy imbalance.Fourcade SMorató LParameswaran JRuiz MRuiz-Cortés TJové MNaudí AMartínez-Redondo PDierssen MFerrer IVillarroya FPamplona RVaquero APortero-Otín MPujol Aaging, axonal degeneration, mitochondria, redox dyshomeostasis, sirtuinSirtuin 2 (SIRT2) is a member of a family of NAD + -dependent histone deacetylases (HDAC) that play diverse roles in cellular metabolism and especially for aging process. SIRT2 is located in the nucleus, cytoplasm, and mitochondria, is highly expressed in the central nervous system (CNS), and has been reported to regulate a variety of processes including oxidative stress, genome integrity, and myelination. However, little is known about the role of SIRT2 in the nervous system specifically during aging. Here, we show that middle-aged, 13-month-old mice lacking SIRT2 exhibit locomotor dysfunction due to axonal degeneration, which was not present in young SIRT2 mice. In addition, these Sirt2 -/- mice exhibit mitochondrial depletion resulting in energy failure, and redox dyshomeostasis. Our results provide a novel link between SIRT2 and physiological aging impacting the axonal compartment of the central nervous system, while supporting a major role for SIRT2 in orchestrating its metabolic regulation. This underscores the value of SIRT2 as a therapeutic target in the most prevalent neurodegenerative diseases that undergo with axonal degeneration associated with redox and energetic dyshomeostasis.WILEY2017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=13070AGING CELLISSN: 14749718ISSNe: 14749726reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déuinstname:Fundació Sant Joan de DéuInglésinfo:eu-repo/semantics/openAccessoai:fsjd.fundanetsuite.com:p130702026-05-27T12:37:41Z
dc.title.none.fl_str_mv Loss of SIRT2 leads to axonal degeneration and locomotor disability associated with redox and energy imbalance.
title Loss of SIRT2 leads to axonal degeneration and locomotor disability associated with redox and energy imbalance.
spellingShingle Loss of SIRT2 leads to axonal degeneration and locomotor disability associated with redox and energy imbalance.
Fourcade S
aging, axonal degeneration, mitochondria, redox dyshomeostasis, sirtuin
title_short Loss of SIRT2 leads to axonal degeneration and locomotor disability associated with redox and energy imbalance.
title_full Loss of SIRT2 leads to axonal degeneration and locomotor disability associated with redox and energy imbalance.
title_fullStr Loss of SIRT2 leads to axonal degeneration and locomotor disability associated with redox and energy imbalance.
title_full_unstemmed Loss of SIRT2 leads to axonal degeneration and locomotor disability associated with redox and energy imbalance.
title_sort Loss of SIRT2 leads to axonal degeneration and locomotor disability associated with redox and energy imbalance.
dc.creator.none.fl_str_mv Fourcade S
Morató L
Parameswaran J
Ruiz M
Ruiz-Cortés T
Jové M
Naudí A
Martínez-Redondo P
Dierssen M
Ferrer I
Villarroya F
Pamplona R
Vaquero A
Portero-Otín M
Pujol A
author Fourcade S
author_facet Fourcade S
Morató L
Parameswaran J
Ruiz M
Ruiz-Cortés T
Jové M
Naudí A
Martínez-Redondo P
Dierssen M
Ferrer I
Villarroya F
Pamplona R
Vaquero A
Portero-Otín M
Pujol A
author_role author
author2 Morató L
Parameswaran J
Ruiz M
Ruiz-Cortés T
Jové M
Naudí A
Martínez-Redondo P
Dierssen M
Ferrer I
Villarroya F
Pamplona R
Vaquero A
Portero-Otín M
Pujol A
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv aging, axonal degeneration, mitochondria, redox dyshomeostasis, sirtuin
topic aging, axonal degeneration, mitochondria, redox dyshomeostasis, sirtuin
description Sirtuin 2 (SIRT2) is a member of a family of NAD + -dependent histone deacetylases (HDAC) that play diverse roles in cellular metabolism and especially for aging process. SIRT2 is located in the nucleus, cytoplasm, and mitochondria, is highly expressed in the central nervous system (CNS), and has been reported to regulate a variety of processes including oxidative stress, genome integrity, and myelination. However, little is known about the role of SIRT2 in the nervous system specifically during aging. Here, we show that middle-aged, 13-month-old mice lacking SIRT2 exhibit locomotor dysfunction due to axonal degeneration, which was not present in young SIRT2 mice. In addition, these Sirt2 -/- mice exhibit mitochondrial depletion resulting in energy failure, and redox dyshomeostasis. Our results provide a novel link between SIRT2 and physiological aging impacting the axonal compartment of the central nervous system, while supporting a major role for SIRT2 in orchestrating its metabolic regulation. This underscores the value of SIRT2 as a therapeutic target in the most prevalent neurodegenerative diseases that undergo with axonal degeneration associated with redox and energetic dyshomeostasis.
publishDate 2017
dc.date.none.fl_str_mv 2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=13070
url https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=13070
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv WILEY
publisher.none.fl_str_mv WILEY
dc.source.none.fl_str_mv AGING CELL
ISSN: 14749718
ISSNe: 14749726
reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
instname:Fundació Sant Joan de Déu
instname_str Fundació Sant Joan de Déu
reponame_str r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
collection r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812429

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